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EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update.
No full text20.500.12530/87861Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several randomised clinical trials have been published that have the potential to change clinical care and support the need for an update. Using EULAR standardised operating procedures, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 16 countries. We modified existing recommendations and created new recommendations. Four overarching principles and 17 recommendations were formulated. We recommend biopsies and ANCA testing to assist in establishing a diagnosis of AAV. For remission induction in life-threatening or organ-threatening AAV, we recommend a combination of high-dose glucocorticoids (GCs) in combination with either rituximab or cyclophosphamide. We recommend tapering of the GC dose to a target of 5 mg prednisolone equivalent/day within 4-5 months. Avacopan may be considered as part of a strategy to reduce exposure to GC in granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Plasma exchange may be considered in patients with rapidly progressive glomerulonephritis. For remission maintenance of GPA/MPA, we recommend rituximab. In patients with relapsing or refractory eosinophilic GPA, we recommend the use of mepolizumab. Azathioprine and methotrexate are alternatives to biologics for remission maintenance in AAV. In the light of recent advancements, these recommendations provide updated guidance on AAV management. As substantial data gaps still exist, informed decision-making between physicians and patients remains of key relevance
Successful valve-in-valve replacement using intravascular lithotripsy for femoral access in an elderly patient with critical aortic stenosis and extensive vascular calcification.
No full text20.500.12530/8785
Identifying and addressing mentorship gaps in European trauma and emergency surgical training. Results from the Young European Society of Trauma and Emergency Surgery (yESTES) mentorship survey.
No full text20.500.12530/87858European training pathways for surgeons dedicated to treating severely injured and critically ill surgical patients lack a standardized approach and are significantly influenced by diverse organizational and cultural backgrounds. This variation extends into the realm of mentorship, a vital component for the holistic development of surgeons beyond mere technical proficiency. Currently, a comprehensive understanding of the mentorship landscape within the European trauma care (visceral or skeletal) and emergency general surgery (EGS) communities is lacking. This study aims to identify within the current mentorship environment prevalent practices, discern existing gaps, and propose structured interventions to enhance mentorship quality and accessibility led by the European Society for Trauma and Emergency Surgery (ESTES). Utilizing a structured survey conceived and promoted by the Young section of the European Society of Trauma and Emergency Surgery (yESTES), we collected and analyzed responses from 123 ESTES members (both surgeons in practice and in training) across 20 European countries. The survey focused on mentorship experiences, challenges faced by early-career and female surgeons, the integration of non-technical skills (NTS) in mentorship, and the perceived role of surgical societies in facilitating mentorship. Findings highlighted a substantial mentorship experience gap, with 74% of respondents engaging in mostly informal mentorship, predominantly centered on surgical training. Notably, mentorship among early-career surgeons and trainees was less reported, uncovering a significant early-career gap. Female surgeons, representing a minority within respondents, reported a disproportionately poorer access to mentorship. Moreover, while respondents recognized the importance of NTS, these were inadequately addressed in current mentorship practices. The current mentorship input of surgical societies, like ESTES, is viewed as insufficient, with a call for structured programs and initiatives such as traveling fellowships and remote mentoring. Our survey underscores critical gaps in the current mentorship landscape for trauma and EGS in Europe, particularly for early-career and female surgeons. A clear need exists for more formalized, inclusive mentorship programs that adequately cover both technical and non-technical skills. ESTES could play a pivotal role in addressing these gaps through structured interventions, fostering a more supportive, inclusive, and well-rounded surgical community
Serum biomarkers at disease onset for personalized therapy in multiple sclerosis.
No full text20.500.12530/87854The potential for combining serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels to predict worsening disability in multiple sclerosis remains underexplored. We aimed to investigate whether sNfL and sGFAP values identify distinct subgroups of patients according to the risk of disability worsening and their response to disease-modifying treatments (DMTs). This multicentre study, conducted across 13 European hospitals, spanned from 15 July 1994 to 18 August 2022, with follow-up until 26 September 2023. We enrolled patients with multiple sclerosis who had serum samples collected within 12 months from disease onset and before initiating DMTs. Multivariable regression models were used to estimate the risk of relapse-associated worsening (RAW), progression independent of relapse activity (PIRA) and Expanded Disability Status Scale (EDSS) score of 3. Of the 725 patients included, the median age was 34.2 (interquartile range, 27.6-42.4) years, and 509 patients (70.2%) were female. The median follow-up duration was 6.43 (interquartile range, 4.65-9.81) years. Higher sNfL values were associated with an elevated risk of RAW [hazard ratio (HR) of 1.45; 95% confidence interval (CI) 1.19-1.76;
Consensus Report and Recommendations on the Management of Late-stage Internal Derangement of the Temporomandibular Joint.
No full text20.500.12530/87855Introduction: This report investigates late-stage internal derangement (ID) of the temporomandibular joint (TMJ) with the aim of establishing a more effective and personalized treatment protocol to improve patients' quality of life (QoL). Material and methods: A consensus was reached among maxillofacial surgeons specializing in LSID, based on a literature research and collective expert experience following the Delphi method. Consensus was considered to be achieved when a response received at least 80% of votes. Results: Four expert groups were established, respectively, focusing on diagnosis, minimally invasive surgery (MIS), open surgery and joint replacement. A comprehensive approach to late-stage ID of the TMJ requires a consensus report. This underscores the need for a personalized treatment plan, considering the variability in clinical presentations and progression of this pathology. Our recommendations aim to optimize clinical outcomes and enhance patient QoL
The overexpression of human amylin in pancreatic β cells facilitate the appearance of amylin aggregates in the kidney contributing to diabetic nephropathy.
No full textDiabetic nephropathy is one of the most frequent complications of diabetic patients and is the leading cause of end-stage renal disease worldwide. The complex physiopathology of this complication raises a challenge in the development of effective medical treatments. Therefore, a better understanding of this disease is necessary for producing more targeted therapies. In this work we propose human amylin as a possible mediator in the development of diabetic nephropathy. Islet amyloid polypeptide or amylin is a hormone co-secreted with insulin. The human isoform has the ability to fold and form amyloid aggregates in the pancreas of patients with type 2 diabetes mellitus, disrupting cellular homeostasis due to its ability to form pores in lipid bilayers. It has been described that hIAPP can be secreted and exported in extracellular vesicles outside the pancreas, being a plausible connecting mechanism between the β-cell and other peripheral tissues such as the kidney. Here, we demonstrate that tubular, podocytes and mesangial cells can incorporate hIAPP coming from β-cells. Then, this hIAPP can form aggregates inside these kidney cells, contributing to its failure. In order to study the consequences in vivo, we found amylin aggregates in the kidney of mice overexpressing hIAPP after feeding a high fat diet. In addition, we observed an increase in glomerulosclerosis index and inflammation. Specifically, there were significant changes in signalling pathways directly involved in the diabetic nephropathy such as an increased in mTORC1 signaling pathway, an alteration in mitochondrial dynamics and an increased in endoplasmic reticulum stress. All these results demonstrate the importance of hIAPP in the kidney and its possible contribution in the development of diabetic nephropathy
First-line therapy with palbociclib in patients with advanced HR+/HER2- breast cancer: The real-life study PALBOSPAIN.
No full text20.500.12530/87908To evaluate the efficacy and safety of first-line therapy with palbociclib in a Spanish cohort treated after palbociclib approval. PALBOSPAIN is an observational, retrospective, multicenter study evaluating real-world patterns and outcomes with 1 L palbociclib in men and women (any menopausal status) with advanced HR+/HER2- BC diagnosed between November 2017 and November 2019. The primary endpoint was real-world progression-free survival (rw-PFS). Secondary endpoints included overall survival (OS), the real-world response rate (rw-RR), the clinical benefit rate, palbociclib dose reduction, and safety. A total of 762 patients were included. The median rw-PFS and OS were 24 months (95% CI 21-27) and 42 months (40-not estimable [NE]) in the whole population, respectively. By cohort, the median rw-PFS and OS were as follows: 28 (95% CI 23-39) and 44 (95% CI 38-NE) months in patients with de novo metastatic disease, 13 (95% CI 11-17) and 36 months (95% CI 31-41) in patients who experienced relapse 12 months after the end of ET. rw-PFS and OS were longer in patients with oligometastasis and only one metastatic site and those with non-visceral disease. The most frequent hematologic toxicity was neutropenia (72%; grade ≥ 3: 52.5%), and the most common non-hematologic adverse event was asthenia (38%). These findings, consistent with those from clinical trials, support use of palbociclib plus ET as 1 L for advanced BC in the real-world setting, including pre-menopausal women and men. NCT04874025 (PALBOSPAIN). Date of registration: 04/30/2021 retrospectively registered
Qualitative evaluation of survey questions to assess treatment preference for daily oral or long‑acting injectable antiretroviral therapy among people living with HIV.
No full textTreatment of HIV has historically required taking daily oral antiretroviral therapy (ART). A recent alternative to daily oral ART is long-acting injectable ART with cabotegravir plus rilpivirine, administered monthly or every 2 months. The purpose of this qualitative study was to evaluate the concept relevance and interpretability of five previously developed questions: one treatment preference question and four questions designed to assess how the emotional burden associated with HIV treatment impacts treatment preferences. Thirty adults in the United States currently receiving HIV treatment were enrolled in a cross-sectional study involving one-on-one concept confirmation and cognitive debriefing interviews. Concept confirmation interviews included topics, questions, and probes designed to elicit information about the emotional burden of HIV and current perceptions of a participant's treatment regimen. Cognitive debriefing assessed the relevance and clarity of instructions, questions, response options, and recall periods. Transcripts were analyzed with MAXQDA. Mean age of participants was 49 years (range: 29-68), with 60% being male and 40% female. Racial demographics included Blacks (40%), Whites (40%), and other (20%). During concept confirmation, participants endorsed concepts relevant to HIV treatment preference: fear of disclosure of HIV status (47%), forgetting to take daily oral medication (40%), and current treatment regimen as a bothersome daily reminder of HIV status (40%). During cognitive debriefing, participants interpreted the instructions, question, response options, and recall periods as intended for the treatment preference question. Additionally, participants confirmed that the preference question's response options were appropriate and relevant to the experiences of people living with HIV. Participants also consistently interpreted the questions related to fear of disclosure of HIV status, anxiety associated with forgetting to take HIV medication, and HIV medication being an uncomfortable reminder of HIV status; however, participants provided variable responses to the question designed to assess treatment ease of use. These results support the concept relevance and interpretability of the single treatment preference question and three of the four emotional well-being questions among adults living with HIV
A modified Delphi exercise in physician-perceived risk factors for drug-induced pneumotoxicity in patients with rheumatological disease.
No full textDrugs used to treat rheumatic disease are associated with pneumotoxicity (drug-induced lung disease), but little is known about associated risk factors. To determine expert physician-perceived risk factors for developing pneumotoxicity in patients with rheumatologic conditions. A modified international 3-tier Delphi exercise was performed. Tier 1 determined patient and drug variables that physicians perceive to be risk factors. Tier 2 determined degree of risk associated with the Tier-1 derived variables. Tier 3 aimed to internally validate and stratify exemplar cases into risk categories. 134 pulmonologists and 49 rheumatologists responded to Tier 1;157 physicians completed all tiers. Perceived risk factors included: drug type; history of previous pneumotoxicity; age; smoking; underlying rheumatic disease type and activity; renal function; pulmonary hypertension; left ventricular failure;presence, nature, severity and progression of pre-existing interstitial lung disease. Tier 2 data stratified these variables into risk profiles e.g. never versus current smoking was perceived as low and high risk respectively. An example of perceived high risk resulting from Tier 3 is a 75-year-old current smoker with high-activity rheumatoid arthritis (RA) with severe, progressive ILD being started on methotrexate. A perceived low risk is a 75-year-old currentsmoker with moderate-activity RA and emphysema with no cardiac or renal disease and no pre-existing ILD being started on rituximab. A risk prediction scoring tool is being developed to be used in validation studies. This modified Delphi exercise defined and stratified the perceived risk factors for developing pneumotoxicity. Age, current smoking, high underlying rheumatological disease activity, HRCT definite UIP and honeycombing, severity and progression of pre-existing ILD were perceived to be the highest risk-factors
Management of cytomegalovirus in adult solid organ transplant patients: GESITRA-IC-SEIMC, CIBERINFEC, and SET recommendations update.
No full text20.500.12530/87852Cytomegalovirus (CMV) infection remains a significant challenge in solid organ transplantation (SOT). The last international consensus guidelines on the management of CMV in SOT were published in 2018, highlighting the need for revision to incorporate recent advances, notably in cell-mediated immunity monitoring, which could alter the current standard of care. A working group including members from the Group for the Study of Infection in Transplantation and the Immunocompromised Host (GESITRA-IC) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Transplantation (SET), developed consensus-based recommendations for managing CMV infection in SOT recipients. Recommendations were classified based on evidence strength and quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The final recommendations were endorsed through a consensus meeting and approved by the expert panel